1. Field of the Invention
The present invention relates generally to a drug delivery apparatus and method for selectively and locally delivering a drug to internal body tissue. More specifically, the present invention relates to an apparatus and method for providing a net flow of electrical current in a desired direction for iontophoresis in conjunction with a catheter to selectively and locally deliver a drug to internal body tissue.
2. Description of the Related Art
Many techniques exist for delivering drugs or other medicaments to body tissue. These include, among others, oral administration, injection directly into body tissue such as through an intramuscular injection or the like, topical or transcutaneous administration where the drug is passively absorbed, or caused to pass, into or across the skin or other surface tissue and intravenous administration which involves introducing a selected drug directly into the blood stream.
Except for topical or transcutaneous administration, the above drug delivery systems tend to be systemic. In other words, administration of the drug is delivered throughout the body by the blood stream. Although transcutaneous drug delivery systems tend to be localized delivery systems in that the drug is delivered locally to a selected area, such drug delivery systems are also, by definition, limited to application of a drug externally through the patient's skin or other surface tissue. Thus, the above described drug delivery systems are generally not appropriate for the localized treatment of internal body tissue.
Although many medical situations are satisfactorily treated by the general systemic administration of a drug, there are many treatments which could be facilitated and/or improved by the ability to deliver or administer a drug locally to a selected portion of internal body tissue, without appreciably affecting the surrounding tissue.
One example is the ability to treat the dilated vessel in percutaneous transluminal coronary angioplasty (PTCA), and thus limit or prevent restenosis. In PTCA, catheters are inserted into the cardiovascular system under local anesthesia and an expandable balloon portion is then inflated to compress the atherosclerosis and dilate the lumen of the artery. Despite the general success of such PTCA procedures, high restenosis rates (reported to be as high as 47%) continue to be a major problem. Various techniques have been tried to treat stenosed vessels including the use of lasers, application of heat and the use of intravascular stents. However, many of these are still under investigation with mixed results, while others have generally not been successful. The ability to administer a drug locally to the dilated portion of the artery in PTCA procedures, without significantly affecting other tissues, would greatly enhance the ability to address the restenosis problem.
A second example of specific application for a local drug delivery system for delivering a drug to an internal body tissue is in the treatment of cancerous tumors or the like. In the treatment of such tumors, an objective is to administer the drug so that it localizes, as much as possible, in the tumor itself. Such drugs are commonly administered systemically through the blood stream. Various means are then utilized for causing the drug to localize in the cancer tumor. Nevertheless, significant portions of the drug still circulate through the blood stream, thereby affecting noncancerous tissue, producing undesirable side effects, and limiting the dosages of the drug which can be safely administered.
Also known is the use of electrophoresis (iontophoresis) to enhance transdermal drug delivery. Known techniques of transdermal iontophoresis have used direct current to promote the delivery of ionic molecules across the skin. In addition, internal iontophoretic drug delivery methods have also disclosed the use of an unspecified source of direct current as well. See, for example, U.S. Pat. No. 5,041,107 to Heil and SU-1069827 to IevIev.
Problems are, however, associated with introducing an electrical current into the body, including muscle stimulation and contraction as well as pain or other unwanted sensations. More importantly, the problem of cardiac arrhythmia (irregular rhythm) can easily arise when electrical current passes through the heart. The current source causing that problem can originate from an external source, within the heart itself, or adjacent to the heart--such as from a coronary artery.
It is known that intensity (current density), frequency, waveform and duration of the electrical current used in iontophoresis have an effect on whether cardiac arrhythmias and other problems will occur as well as the magnitude of those reactions. The threshold at which ventricular fibrillation occurs with various transthoracic and intracardiac electrical levels is known to increase with higher frequency currents (i.e., greater than 100 Hz). The threshold of sensation also increases with higher frequencies. The above observations were made using a sinusoidal alternating current set at various frequencies.
The use of alternating current to accomplish drug delivery through iontophoresis is, however, not very effective. By its very nature, a sinusoidal alternating current has increasing and decreasing current, to the point where flow can stop or actually reverse direction, thereby hampering the drug delivery effect.
One attempt to minimize the risk of iontophoresis-induced arrhythmias is disclosed in U.S. Pat. No. 5,087,243. An implanted myocardial iontophoresis patch system is disclosed there in which a pulsed current is supplied to the anodal patch. The pulses are synchronized with ventricular depolarization to avoid the interval during which the heart is vulnerable to electrically induced arrhythmias or unnatural heart rhythms. To accomplish that, the system requires instrumentation to sense the natural heartbeat of the patient. In addition, even these precautions may not prevent arrhythmias if higher iontophoretic currents are used (e.g., greater than 1 mA/cm.sup.2). Also, the disclosed preferred 80-100 msec pulses will not prevent vascular muscle stimulation resulting in vaso-constriction and may cause other unwanted stimulation or sensations.
Accordingly, there is a need in the art for a method and apparatus for delivering a drug selectively and locally to internal body tissue using iontophoresis in conjunction with a catheter, without significantly affecting other tissue or inducing cardiac arrhythmias or other unwanted effects. There is a further need for such a system and method for the localized treatment of internal body tissues to limit restenosis following PTCA, to treat cancerous tumors or the like, or to treat various other medical situations using iontophoresis in conjunction with a catheter, without inducing vascular stimulation and spasms, cardiac arrhythmias or other unwanted effects.